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Quantitative research on the social, demographic, and economic outcomes of sexual minorities has long been hampered by data shortfalls, with most surveys and censuses limited by sample sizes and/or a lack of direct questions on sexual identity. The growing availability of administrative data presents an opportunity to fill some of these gaps. This article highlights the challenges and opportunities involved with using a novel administrative dataset--the Longitudinal Administrative Databank, which includes 20% of Canadian tax filers--to study sexual minority populations in Canada. We identify three sources of bias, propose strategies to adjust for this bias, and introduce a measure of \"inferred sexual minority status\" to improve the identification of sexual minorities in tax data. Administrative tax data offers significant advantages, including a large sample size, high-quality income data for individuals and linked family members, a longitudinal design, and the ability to trace individuals' same-/different-sex partnership histories. Our adjustment strategies mitigate some biases in identifying same-sex couples, including underreporting, misclassification, and measurement errors. The estimated proportion of individuals in same-sex marriages closely aligns with Canadian census estimates from 2006-2021, while the proportion in same-sex common-law partnerships is underestimated. Finally, our earnings gaps analyses highlight the utility of the inferred sexual minority status measure.

Sohrab Shah, Samuel Aparicio and colleagues analyze whole genomes and single cells from ovarian cancers in the peritoneal cavity to establish patterns of disease spread. They determine the clonal relationships between multiple tumor sites and characterize the migratory potential of genomically diverse clones. We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers.

BACKGROUND Across the globe, employment for pay outside the home plays a key role in the lives of women, and increasing the proportion of women involved in high-quality jobs is a critical component of reaching several sustainable development goals. While existing research from high-income societies demonstrates that women's employment is not constant over the life course, relatively less is known about women's employment trajectories in lowincome countries. OBJECTIVE We examine employment trajectories among women in rural Nepal, accounting for job type, employment intensity, and earnings. METHODS Using eight years of quarterly employment data from the 2016 Female Labor Force Participation and Child Outcomes Study component of the Chitwan Valley Family Study, we identify typologies of employment trajectories by conducting sequence and cluster analyses. RESULTS First, half of the women in our sample were never employed in the study period. Second, among women who were ever employed, there were considerable transitions into and out of the workforce. Third, women's employment trajectories are largely determined by job type (wage labor, salaried jobs, and self-employment), with little movement across job types. Additionally, self-employed women and those with salaried jobs had higher earnings and higher employment intensity than women with wage labor jobs. CONCLUSIONS We see intense stratification into job types, including no employment at all, and substantial transitions into and out of the workforce among workers. Women experience many employment disruptions over the life course, with little sign of upward employment mobility. CONTRIBUTION This study provides new empirical portraits of women's employment in low-income settings by investigating the multiple dimensions of women's employment from a life course perspective.

OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies. We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 \"ovarian cancer\" cell lines has been classified into histotypes using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis. Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA) and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements. As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histotype of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic \"ovarian carcinoma\" cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of SKOV3 and A2780 as models of high-grade serous carcinoma.

Objective This study examines how marriage‐cohabitation gaps in household specialization (labor supply and earnings) vary across institutional contexts for same‐sex couples (SSCs) and different‐sex couples (DSCs) in Canada. Background Prior research suggests that marriage‐cohabitation gaps are smaller in contexts where cohabitation is more prevalent, but it has overlooked how legal protections (at the contextual level) and gender composition (at the couple level) moderate this association. As a result, little is known about whether differences in household specialization stem from heightened gendered expectations attached to marriage or stronger legal protections for married couples. This study posits that marriage‐cohabitation gaps will be larger in contexts where legal protections for cohabitors are less marriage‐like. Methods Using the 2006 and 2016 Canadian Census and the 2011 National Household Survey, I estimate ordinal and fractional logit models to examine marriage‐cohabitation gaps in specialization among all couples (N = 2,788,055) and couples with young children (N = 826,305). Results Among DSCs, marriage‐cohabitation gaps were larger in Québec than in English Canada vis‐à‐vis earnings but not labor supply. Patterns among SSCs were more heterogeneous: gaps in labor supply were larger in English Canada for female couples but larger in Québec for male couples. Gaps in earnings were generally larger in Québec, with few exceptions. However, DSCs consistently specialized more than SSCs. Conclusion While existing research suggests marriage‐cohabitation gaps in household specialization are largely explained by the prevalence of cohabitation, my results indicate that legal protections (at the contextual level) and gender composition (at the couple level) play a more decisive role.

Ovarian endometrioid carcinomas and endometrial endometrioid carcinomas share many histological and molecular alterations. These similarities are likely due to a common endometrial epithelial precursor cell of origin, with most ovarian endometrioid carcinomas arising from endometriosis. To directly compare the mutation profiles of two morphologically similar tumor types, endometrial endometrioid carcinomas (n=307) and ovarian endometrioid carcinomas (n=33), we performed select exon capture sequencing on a panel of genes: ARID1A, PTEN, PIK3CA, KRAS, CTNNB1, PPP2R1A, TP53. We found that PTEN mutations are more frequent in low-grade endometrial endometrioid carcinomas (67%) compared with low-grade ovarian endometrioid carcinomas (17%) (P<0.0001). By contrast, CTNNB1 mutations are significantly different in low-grade ovarian endometrioid carcinomas (53%) compared with low-grade endometrial endometrioid carcinomas (28%) (P<0.0057). This difference in CTNNB1 mutation frequency may be reflective of the distinct microenvironments; the epithelial cells lining an endometriotic cyst within the ovary are exposed to a highly oxidative environment that promotes tumorigenesis. Understanding the distinct mutation patterns found in the PI3K and Wnt pathways of ovarian and endometrial endometrioid carcinomas may provide future opportunities for stratifying patients for targeted therapeutics.

Research on marriage values bears crucial policy implications in a low-fertility context where obstacles to marriage are indicative of fertility barriers, particularly when non-marital births are rare. Using multiple waves of the Taiwan Social Change Survey between 1985 and 2015, this study explores the attitudinal shifts in marriage during a time of rapid social change. The findings indicate that substantial changes have taken place with regard to the institution of marriage. A cohort replacement effect, as well as intra-cohort changes, are the main drivers for the majority of changes in attitudes toward marriage. Overall, more people in the general public now believe that marriages do not necessarily bring more happiness and satisfaction to one’s life. More of them increasingly believe that conventional norms imposed on married couples, and women in particular, should be relaxed. These include norms about living arrangements, in-law relationships, divorce, and the importance of childbearing. However, preferences for marital births have changed little, and more people in the 2010s endorse the notion of having at least one son to continue the family lineage, than in the 1990s. These seemingly paradoxical patterns of value liberalisation and traditional fertility preferences, along with rising female autonomy, could make the “marriage package” seem less desirable for younger cohorts of economically independent women, leading to delayed (or even foregone) family formation.

Background Mucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors. Our goals were to establish the overall frequency of cancer-hotspot mutations across a large cohort, especially those tumors previously thought to be “RAS-pathway alteration negative”, using highly-sensitive next-generation sequencing as well as further explore a small number of cases with apparent heterogeneity in RAS-pathway activating alterations. Methods Using the Ion Torrent PGM platform, we performed next generation sequencing analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2-amplification status were sequenced independently for two mucinous carcinoma (MC) cases, previously established as showing ERBB2 amplification/overexpression heterogeneity, to assess the hypothesis of subclonal populations containing either KRAS mutation or ERBB2 amplification independently or simultaneously. Results We detected mutations in KRAS , TP53 , CDKN2A , PIK3CA , PTEN , BRAF , FGFR2 , STK11 , CTNNB1 , SRC , SMAD4 , GNA11 and ERBB2. KRAS mutations remain the most frequently observed alteration among MC (64.9 %) and mucinous borderline tumors (MBOT) (92.3 %). TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68 % of MC and as many as 20 % of MBOT. Proven and potential RAS-pathway activating changes were observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were observed in a substantial number of cases (7/63 total), as was co-occurrence of KRAS and BRAF mutations (one case). Microdissection of ERBB2 -amplified regions of tumors harboring KRAS mutation suggests these alterations are occurring in the same cell populations, while consistency of KRAS allelic frequency in both ERBB2 amplified and non-amplified regions suggests this mutation occurred in advance of the amplification event. Conclusions Overall, the prevalence of RAS-alteration and striking co-occurrence of pathway “double-hits” supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations.

A single, recurrent somatic point mutation (402C→G) in FOXL2 has been described in almost all adult-type granulosa cell tumors but not other ovarian neoplasms. Histopathological features of adult-type granulosa cell tumors can be mimicked by a variety of other tumors, making diagnosis of adult-type granulosa cell tumor challenging. It has been suggested that molecular testing for FOXL2 mutation might be a useful tool in the diagnosis of adult-type granulosa cell tumors. The aim of this study was to demonstrate how testing for the FOXL2 mutation can be used in a gynecological pathology consultation service and to establish clear procedural guidelines for FOXL2 testing. Immunohistochemistry for FOXL2 was done using an anti-FOXL2 polyclonal antiserum. If immunohistochemistry was positive, FOXL2 mutation status was subsequently analyzed using a TaqMan assay. A dilution experiment was done to assess the sensitivity and minimum tumor cellularity requirements for our TaqMan assay. Twenty problematic cases were assessed, where the differential diagnosis after the initial investigations included adult-type granulosa cell tumors. Differential diagnoses included: thecoma, Sertoli–Leydig cell tumor, juvenile granulosa cell tumor, endometrial stromal sarcoma and others. In all cases, FOXL2 immunohistochemistry was positive and in six samples the FOXL2 mutation was detected, thus confirming a diagnosis of adult-type granulosa cell tumor. The TaqMan assay was able to reliably detect the FOXL2 mutation with input DNA in the range of 2.5–20 ng, and with a minimum of 25% tumor cell nuclei. The analysis of the FOXL2 mutational status in clinical samples is a useful diagnostic tool in situations where the differential diagnosis is between adult-type granulosa cell tumor and other ovarian tumors. The TaqMan assay requires a minimum of 2.5 ng DNA, with optimal assay performance for 5 to 10 ng DNA input. Laser capture or needle-macrodissection should be undertaken to enrich samples with tumor cell content below 25%.

Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations. A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire was used to identify normal controls aged 4-15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes (D4 dopamine receptor, DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire. A total of 97 children with doctor-diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57±0.73 vs. 1.73±0.77 μg/dL, p = 0.15). No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects (4.52±3.22 μg/g cr. vs. 4.64±2.95 μg/g cr., p = 0.43). ADHD was significantly more prevalent among males in this study (male to female ratio: 5:1 for the ADHD group and 1.3:1 for the control group, p<0.01). The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants. This study indicated that NP exposure might not promote ADHD in children, even though children in Taiwan had relatively high levels of NP compared to those reported previously and those in developed nations.